Primary liver cancer (PLC) may be mainly classified as the following four types: hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), hepatoblastoma (HB), and combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (cHCC-ICC). The majority of PLC develops in the background of tumor microenvironment, such as inflammatory microenvironments caused by viral hepatitis, alcoholic or nonalcoholic steatohepatitis, carbon tetrachloride (CCl), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), and necroptosis-associated hepatic cytokine microenvironment caused by necroptosis of hepatocytes. However, the impact of different types of microenvironments on the phenotypes of PLC generated by distinct oncogenes is still unclear. In addition, the cell origin of different liver cancers have not been clarified, as far as we know. Recent researches show that mature hepatocytes retain phenotypic plasticity to differentiate into cholangiocytes. More importantly, our results initially demonstrated that HCC, ICC, and cHCC-ICC could originate from mature hepatocytes rather than liver progenitor cells (LPCs), hepatic stellate cells (HSCs) and cholangiocytes in AKT-driven, AKT/NICD-driven and AKT/CAT-driven mouse PLC models respectively by using hydrodynamic transfection methodology. Therefore, liver tumors originated from mature hepatocytes embody a wide spectrum of phenotypes from HCC to CC, possibly including cHCC-ICC and HB. However, the underlying mechanism determining the cancer phenotype of liver tumors has yet to be delineated. In this review, we will provide a summary of the possible mechanisms for directing the cancer phenotype of liver tumors (i.e., ICC, HCC, and cHCC-ICC) in terms of oncogenic driver genes and tumor microenvironment. Moreover, this study initially revealed the cell origin of different types of liver cancer.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198508 | PMC |
http://dx.doi.org/10.1038/s41419-020-2509-x | DOI Listing |
BioDrugs
January 2025
Orsay-Vallée Campus, Paris-Saclay University, Gif-sur-Yvette, France.
Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment.
View Article and Find Full Text PDFClin Exp Med
January 2025
Department of Thoracic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Introduction Recently, immune cells within the tumor microenvironment (TME) have become crucial in regulating cancer progression and treatment responses. The dynamic interactions between tumors and immune cells are emerging as a promising strategy to activate the host's immune system against various cancers. The development and progression of hepatocellular carcinoma (HCC) involve complex biological processes, with the role of the TME and tumor phenotypes still not fully understood.
View Article and Find Full Text PDFClin Transl Oncol
January 2025
Department of General Surgery, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510013, Guangdong, China.
Introduction: The transporter associated with antigen processing (TAP) is a key component of the classical HLA I antigen presentation pathway. Our previous studies have demonstrated that the downregulation of TAP1 contributes to tumor progression and is associated with an increased presence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. However, it remains unclear whether the elevation of MDSCs leads to immune cell exhaustion in tumors lacking TAP1.
View Article and Find Full Text PDFArch Dermatol Res
January 2025
Department of Dermatology, The University of Sydney at Royal Prince Alfred Hospital, Missenden Rd, NSW , Camperdown, 2050, Australia.
Melanoma is an immunogenic tumor. The melanoma tumor immune microenvironment (TIME) is made up of a heterogenous mix of both immune and non-immune cells as well as a multitude of signaling molecules. The interactions between tumor cells, immune cells and signaling molecules affect tumor progression and therapeutic responses.
View Article and Find Full Text PDFHematol Oncol
January 2025
University of California Irvine, Irvine, California, USA.
Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!